Renal disease

Question 1

What are the major functions of the kidney?

Answer 1

• Excretion of metabolic waste products and foreign chemicals - including drugs
• Regulation of fluid, elecrolytes and acid/base balance
• Regulation of blood pressure - renin
• Regulation of calcium and bone metabolism
• Regulation of haematocrit - erythropoeitin

Question 2

Desrcibe the anatomy of the kidneys:

1. Location
2. Landmarks
3. Length
4. Weight
5. Amount of cardiac output
6. Basic unit and what makes it up

Answer 2

1. Retroperitoneal
2. T12 to L3 on left and right is slightly lower
3. Mean length is 11cm
4. Male weight = 125-170g, female weight = 115-155g
5. Recieve 20% of cardiac output
6. Nephron - made up of a glomerlus, afferent and efferent arterioles and tubules

Question 3

Describe the order at which filtrate passes through the nephron

Answer 3

• Blood is filtered at the glomerlus
• The filtrate is modified in the tubules - proximal convoluted tubule, loop of henle, distal convoluted tubule, collecting tubule and finally the collecting duct

Question 4

What is the function of the proximal convoluted tubule?

Answer 4

• PCT actively resorbs sodium
• Hydrogen exchange to allow carbonate resorption
• Co-transport of amino acids, phosphate, glucose
• Potassium is also reabsorbed

Question 5

Describe the function of the Loop of Henle

Answer 5

• Descening/ thin ascending limb is permeable to water but not ions or urea
• Ascending limb actively resorbs sodium and chloride
• Coutercurrent multiplier, aligned wit vasa recta

Question 6

What is the function of the distal convoluted tubule?

Answer 6

• Impermeable to water
• Regulates pH via active transport (H/bicarbonate)
• Regulated sodium, potassium via active transport - aldosterone
• Regulates calcium - through PTH and 1,5-dihydroxycholecalciferol

Question 7

What is the function of the collecting ducts?

Answer 7

• Resorbs water - principal cells and antidiuretic hormone
• Regulates pH - intercalated cells and proton excretion

Question 8

1. What are immune complexes?
2. Whta happens to immune complexes in the kidney?

Answer 8

1. An immune complex is a latticework of antibody and antigen - may be endogenous or exogenous antigens
2. May deposit in the glomerlus causing an inflammatory response, complement activation and stimulation of inflammatory cells

May deposit at different rates and at different sites

Question 9

What are the different signs and symptoms that occur in renal disease?

Answer 9

• Haematuria
• Proteinuria
• Uraemia
• Hypertension
• Oliguria/Anuria
• Polyuria
• Oedema
• Colic

Question 10

What are the genitourinary malformations and issues that can occur in the kidney?

Answer 10

• Agenesis
• Renal fusion e.g. horse-shoe
• Ectopic kidney
• Renal dysplasia
• Pelvi-ureteric Junction obstruction
• Ureteral duplication
• Vesicoureteral reflux
• Posterior urethral valves

Question 11

Describe adult polycystic kidney disease

1. Inheritance
2. Signs and symptoms
3. Genes involved
4. Complications

Answer 11

1. Mono Dominant inheritance - 1:500
2. Presents in adulthood with hypertension, flank pain and haematuria
3. PKD1, PKDS2
4. 10% risk of end-stage renal failure, PKD patients have a higher risk of developing Berry aneurysms and a higher chance of bursting

Question 12

1. When do cysts commonly develop?
2. What is there an increased risk of when cysts develop?

Answer 12

1. Cysts commonly develop in patients with end stage renal disease who are on dialysis - often they are multiple, bilateral and can be cortical or medullary
2. There is an increased risk of development of malignancy - 7% at 10 years - most commonly papillary renal cell carcinoma

Question 13

What are the main renal disease syndromes?

Answer 13

• Acute renal failure (Acute kidney injury)
• Nephrotic syndrome
• Isolated Urinary abnormalities
• Chronic kidney disease

Question 14

1. What is acute renal failure?
2. What are the causes of the different types of acute renal failure?

• Pre-renal
• Renal
• Post renal

Answer 14

1. Acute renal failure is a rapid deterioation in renal function (hours-days)

2.

• Pre-renal causes - failure of perfusion of the kidney
• Renal - acute tubular injury, acute glomerulonephritis, thrombotic microangiopathy
• Post-renal - obstruction

Question 15

1. What is acute tubular injury?
2. What can predispose to it?

Answer 15

1. Acute tubular injury is the commonest cause of acute renal failure. Tubular epithelial cells can be damaged by ischaemia, toxins e.g. contrast, Hb, myglobin and drugs
2. Critical illness it is a common occurrence. Drugs that inhibit vasodilatory prostaglandins predispose e.g. NSAIDs

Question 16

1. Describe the pathophysiology of acute tubular injury

Answer 16

1. Ischaemia/toxins/drugs affecting the tubules causes loss of polarity and brush border which is normal. Apoptosis of cells occur, and sloughing of viable and dead cells leading to luminal obstruction. Necrosis occurs and then viable cells spread and dedifferentiate to replace damaged cells

Failure of glomerulation filtration:

• Blockage of tubules by casts
• Leakage of tubules to intestinal space
• Secondary haemodynamic changes

Question 17

1. What is acute tubulo-intestinal nephritis?
2. What causes it?
3. What is the pathogenesis?

Answer 17

1. Acute tubulo-interstitial nephritis is immune injury to tubules and intersitium
2. Can be caused by:

• Infection
• Drugs - NSAIDs, antibiotics, Diuretics, Allopurinol and PPIs
  3. Heavy interstitial inflammatory infiltrate with tubular injury, eosinophil infiltration and granuloma formation

Question 18

1. What is acute Glomerulonephritis?
2. What does it present with?
3. What are crescents?

Answer 18

1. Acute glomerulonephritis is acute inflammation of glomeruli
2. Presents with oliguria with urine casts containing erythrocytes and leucocytes
3. Cresecents are proliferation of cells within the Bowman’s space - sign of acute renal failure

Question 19

1. What is Acute Cresentic glomerulonephritis?
2. What is associated with it?
3. What can it lead to?

Answer 19

1. Acute cresenteric glomerulonephritis is caused by immune complexes. (Seen in anti-glomerular basement membrane diesease. Presence of Pauci-immune or anti-neutrophil cytoplasm antibodies)
2. Aetiologies include SLE, IgA nephropathy and post-infectious glomerulonephritis
3. Leads rapidly to irreversible renal failure

Question 20

1. What is is Anti-glomerular basement membrane disease and what is the pathogenesis?

Answer 20

1. Ant-GBM is a rare and severe disease caused by antibodies directed against the glomerular basement membrane. Affects the C-terminal domain of Type 4 collagen, may cross-react with alveolar basement membrane leading to pulmonary haemorrhage

Linear deposition of IgG demonstratable on glomerular basement membrane

Question 21

1. What is Pauci-immune cresenteric glomerulonephritis?
2. What antibodies is it associated with it?

Answer 21

1. Pauci-immune cresenteric glomerulonephritis is caused by scanty glomerular immunoglobulin deposits
2. Usually ANCA associated which triggers neutrophil activation and glomerular necrosis. Can lead to vasculitis elsewhere

Question 22

1. What is thrombotic microangiopathy and pathophysiology?
2. What are the two types and what causes the two different types?

Answer 22

1. Damage to the endothelium in glomeruli, arterioles, arteries leading to thrombosis. Red cells can be damaged by fibrin which can lead to microangiopathic haemolytic anemia and HUS
2. Types: diarrhoea associated and non-diarrhoea associated

Diarrhoea associated:

• Bacterial gut infection such as with E.coli (hence link with HUS)
• Toxins released that target renal endothelium

Non-diarrhoea associated:

• Defects in regulation of complement
• Deficiency in ADAMTS13
• Drugs e.g. calcineurin inhibitors
• Radiation
• Hypertension
• Scleroderma
• Antiphospholipid syndrome (+/- SLE)

Question 23

1. What is nephrotic syndrome?
2. What are the common signs?
3. What conditions are associated with nephrotic syndrome?

Answer 23

1. Nephrotic syndrome is a breakdown in selectivity of glomerular filtration leading to protein leak
2. Common signs:

Proteinuria (>3.5g/day)

Hypoalbuminemia

Oedema

Hyperlipidemia

3. Associated with:
   - Primary glomerular disease, non-immune complex related e.g. minimal change disease
   - Primary renal disease, immun complex mediated - membranous glomerulonephritis
   - Systemic diseases - diabetes mellitus, amyloidosis and SLE

Question 24

Describe minimal change disease

Answer 24

Minimal change disease is a glomerular disease that leads to large loss of protein in the urine. Is the most common cause of nephrotic syndrome in children

Generally responds to immunosuppression

Question 25

Describe focal segmental glomerulosclerosis

Answer 25

Type of primary glomerular disease leading some glomeruli to become scarred. This can lead to renal failure and protein leakage. Non-immune complex related Cause of nephrotic syndrome in children and adolescents

Question 26

Describe membranous glomerulonephritis including pathogenesis What antibody is associated with the disease?

Answer 26

Membranous glomerulonephritis is a form of primary renal disease and is immune complex mediated. Associated with immune deposits on outside of glomerular basement membrane (supepithelial) Primary disease is autoimmune - in 75% cases the antibody associated is against phospholipase A2 type M receptor (PLA2R) Common cause of nephrotic syndrome in adults

Question 27

1. Describe diabetic nephropathy pathogenesis 2. Describe the stages of nodular glomerulosclerosis in diabetic nephropathy

Answer 27

1. Diabetic nephropathy affects 30-40% of people with diabetes. High glucose levels are directly injurious. Typically starts as microalbuminuria before progression to proteinuria and nephrotic syndrome 2. Nodular Glomerulosclerosis Stage 1- thickening of basement membrane on EM Stage 2 - Increase in mesangial matrix, without nodules Stage 3- Nodular lesions/Kimmelstiel-wilson Stage 4- Advanced glomerulosclerosis

Question 28

1. What is amyloidosis? 2. What are the forms that effect the kidney?

Answer 28

1. Amyloidosis is a rare condition that is caused by the build up of amyloid in the body which can be deposited in any organ. Amyloid is a an extraceullular proteinaceous material exhibiting beta-sheet structure 2. Commonest forms in the kidney are: * AA- Derived from serum amyloid associated protein (SAA), and acute phase protein. Patients tend to have a chronic inflammatory state * AL - derived from immunogloblin light chains, 80% of patients have multiple myeloma

Question 29

What isolated urinary abnormalities can cause microscopic haematuria?

Answer 29

* Thin basement membranes * IgA nephropathy

Question 30

What is Thin Basement Membranes disorder?

Answer 30

* Thin basement membranes is a hereditary defect in Type 4 collagen synthesis, causing basement membranes to be \<250nm thick * Haematuria is the only consequence in most cases

Question 31

What is Alport's syndrome?

Answer 31

Alport's syndrome is a genetic condition associated with progressive loss of kidney function, deafness and ocular disease. X-linked dominant mutation affecting alpha5 subunit Second most common genetic cause of end-stage kidney failure, after PKD.

Question 32

Describe IgA Nephropathy

Answer 32

* Commonest cause of glomerulonephritis * IgA predominant mesangial immune complex deposition * 30% develop end-stage renal failure * Aetiology not fully understood but secondary forms observed in liver, bowel and skin. Can be seen with HSP

Question 33

1. Describe Chronic kidney disease and associated conditions 2. What GFR ml/min denotes end stage renal failure 3. What are the most common causes?

Answer 33

* Can be caused by a range of diseases e.g. diabetes * Association with ischaemic heart disease - hypertension, hyperlipidemia, calcification of blood vessels * Association with calcium and phosphate metabolic derangement - hyperparathyroidism, osteomalacia and osteoporosis 2. \<15ml/min 3. Diabetes, glomerulonephritis and PKD

Question 34

Describe hypertensive nephropathy pathophysiology

Answer 34

Narrowing of arteries leading to scarring and ischaemia of glomeruli. Hypertension in glomeruli leading to altered haemodynamic environment, stress and segmental scarring All this leads to reduced kidney function

Question 35

Describe SLE and how it can affect the kidneys

Answer 35

* SLE is a systemic autoimmune disease that affects kidney, skin, joints, heart, serosal surfaces and CNS * Deposition of immune complexes in the kidney is common * Antinuclear and anti-dsDNA antibodies are typical - antibodies are directed at a broad range of intracellular and extracellular antigens * Depending on the site, speed and intensity of immune complexes deposition, may present as: - Acute renal failure, nephrotic syndrome, isolated urinary abnormality or CKD